title: Expression of human endogenous retrovirus-w including syncytin-1 in cutaneous T-cell lymphoma.
abstract: The pathomechanism of mycosis fungoides (MF), the most common type of primary cutaneous T-cell lymphomas (CTCLs) and a malignancy of non-recirculating, skin-resident T-cells, is unknown albeit underlying viral infections have been sought for. Human endogenous retroviruses (HERVs) are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancers. We explored the transcriptional activity of HERV sequences in a total of 34 samples comprising MF and psoriasis skin lesions, as well as corresponding non-malignant skin using a retrovirus-specific microarray and quantitative RT-PCR. To identify active HERV-W loci, we cloned the HERV-W specific RT-PCR products, sequenced the cDNA clones and assigned the sequences to HERV-W loci. Finally, we used immunohistochemistry on MF patient and non-malignant inflammatory skin samples to confirm specific HERV-encoded protein expression. Firstly, a distinct, skin-specific transcription profile consisting of five constitutively active HERV groups was established. Although individual variability was common, HERV-W showed significantly increased transcription in MF lesions compared to clinically intact skin from the same patient. Predominantly transcribed HERV-W loci were found to be located in chromosomes 6q21 and 7q21.2, chromosomal regions typically altered in CTCL. Surprisingly, we also found the expression of 7q21.2/ERVWE1-encoded Syncytin-1 (Env) protein in MF biopsies and expression of Syncytin-1 was seen in malignant lymphocytes, especially in the epidermotropic ones, in 15 of 30 cases studied. Most importantly, no Syncytin-1 expression was detected in inflammatory dermatosis (Lichen ruber planus) with skin-homing, non-malignant T lymphocytes. The expression of ERVWE1 mRNA was further confirmed in 3/7 MF lesions analyzed. Our observations strengthen the association between activated HERVs and cancer. The study offers a new perspective into the pathogenesis of CTCL since we demonstrate that differences in HERV-W transcription levels between lesional MF and non-malignant skin are significant, and that ERVWE1-encoded Syncytin-1 is expressed in MF lymphoma cells.
authors.affiliation: Department of Dermatology and Allergology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Pilvi
authors.initials: P
authors.lastname: Maliniemi
authors.forename: Michelle
authors.initials: M
authors.lastname: Vincendeau
authors.forename: Jens
authors.initials: J
authors.lastname: Mayer
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Sonja
authors.initials: S
authors.lastname: Hahtola
authors.forename: Leena
authors.initials: L
authors.lastname: Karenko
authors.forename: Emilia
authors.initials: E
authors.lastname: Carlsson
authors.forename: Francois
authors.initials: F
authors.lastname: Mallet
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seifarth
authors.forename: Christine
authors.initials: C
authors.lastname: Leib-Mösch
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
mesh_terms: D016000:Cluster Analysis; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D006801:Humans; D008010:Lichen Planus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000473:pathology; D008297:Male; D009182:Mycosis Fungoides / Q000235:genetics; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C405335:syncytin